The long-term aim of my program is to increase our knowledge of the genes determining the structure of proteins in eukaryotes and the control of their synthesis. In the current five year proposal I plan to initiate comparative studies of the regions of DNA close to genes determining the structures of well-defined proteins having similar functions but potentially differential controls. Two approaches will be used: amino acid sequence studies to delineate the structural genes: DNA cloning experiments to permit potential perigenic control elements to be isolated for subsequent comparisons. Three complex multigene loci have been selected because each is interesting in its own right, each is amenable to one or both approaches, and we have considerable experience with them. Specifically we propose to: 1. characterize some of the amino acid sequence similarities and differences between human HLA antigens determined by alleles at the HL-A and HL-B loci, using our microsequencing procedure already proven to work with these proteins. 2. complete protein structural studies, already initiated, to characterize the products of the independently segregating loci (at least two) which determine corn H1 histones. 3. obtain several independent DNA clones of the corn histone gene complexes to look for differences between the several loci. 4. obtain for comparative purposes DNA clones of mouse non-alpha globin structural genes and their perigenic regions, including if possible those for adult and embyronic chains, from animals with the singlet locus, beta S, and doublet locus, beta D, major plus beta D minor. (We have already cloned mouse globin cDNA.)